Safety of SGI-1776, A PIM Kinase Inhibitor in Refractory Prostate Cancer and Relapsed/Refractory Non Hodgkin's Lymphoma
This study has been terminated.
(The dose limiting toxicity of cardiac QTc prolongation was identifiedin the phase 1 study in patients with refractory prostate and lymphoma)
Information provided by (Responsible Party):
First received: February 19, 2009
Last updated: December 1, 2011
Last verified: December 2011
Patients with hormone and docetaxel refractory prostate cancer or relapsed/refractory non-Hodgkin's lymphoma for which no available standard therapy or therapy which may provide clinical benefit is available will be enrolled. Primary objectives: estimate the maximum tolerated dose and dose-limiting toxicities. Secondary objectives: Response rate, pharmacokinetic and pharmacodynamic profiles, Prostate Specific Antigen response and renal elimination.
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
||Safety Study to Determine the Maximum Tolerated Dose, Pharmacokinetics and Pharmacodynamics of SGI-1776, a PIM Kinase Inhibitor, in Subjects With Hormone and Docetaxel Refractory Prostate Cancer and Relapsed/Refractory Non Hodgkin's Lymphoma
Primary Outcome Measures:
- MTD & DLT [ Time Frame: July 2011 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Response rate, pharmacokinetics, PSA response, renal elimination and pharmacodynamic effects on biomarker modulation. [ Time Frame: July 2011 ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||October 2010 (Final data collection date for primary outcome measure)
Starting dose 100 mg (total daily dose) administer as 50 mg every 12 hours for 14 days of a 21-day cycle, dose escalation in successive cohorts until progression or toxicity develops
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Read, understand and sign the IRB- or IEC-approved ICF confirming his or her willingness to participate in this trial.
- At least 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Adequate bone marrow function; normal renal and hepatic function, normal cardiac function.
- Normal cardiac function in the opinion of the investigator and supported by LVEF 50% or greater on the screening echocardiogram (or MUGA), no significant abnormalities on the screening ECG (eg, left bundle branch block, III degree AV block, acute myocardial infarction, Wolff-Parkinson-White syndrome or QTc interval ≥ 450 msec) and no history of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia or family history of Long QT Syndrome).
- Active secondary malignancy or history of other malignancy within the last two years except non-melanoma skin cancers or cervical carcinoma in situ.
- History of significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure and/or myocardial infarction or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
- Received any anticancer agent(s) within the past 3 weeks, including investigational agents, chemotherapy (6 weeks for nitrosoureas or mitomycin), immunotherapy, biologic or marketed or investigational tyrosine kinase inhibitors.
- Received prior radiation therapy within the past 4 weeks or received irradiation of ≥ 25% of their bone marrow reserve.
- Any serious, uncontrolled active infection that requires systemic treatment or known infection with HIV, HCV or HBV.
- Symptomatic CNS metastases or lesions for which treatment is required.
- Males with histologically confirmed adenocarcinoma of the prostate, which is now metastatic (e.g., any T, any N, M1a-c)based on bone scan, CT scan, or MRI scan. Demonstrated evidence of progressive disease despite androgen deprivation (androgen ablation or surgical castration), anti-androgen withdrawal and progression of disease after docetaxel-based therapy.
Demonstrated evidence of progressive disease despite androgen deprivation (androgen ablation or surgical castration), anti-androgen withdrawal and progression of disease after docetaxel-based therapy.
• Greater than 25% increase in 3 consecutive tests (PSA 1 < PSA 2 < PSA 3), each PSA value separated by at least 1 week
- Serum testosterone level ≤ 50 ng/dL post orchiectomy or while maintained on continuous or intermittent medical androgen suppression with a LHRH agonist or antagonist.
- At least 4 weeks since prior flutamide, megestrol, ketoconazole, aminoglutethimide; and at least 6 weeks since prior bicalutamide or nilutamide.
- Systemic corticosteroids discontinued within two weeks of dosing, except low dose regimens which may continue if unchanged
- Strontium-89 or Samarium-153 must have been completed at least 8 weeks prior to the first dose of therapy and recovered from all treatment-related toxicities.
1. Must not be receiving concurrent anti-androgen hormonal therapy for hormone refractory prostate cancer.
- Histologically proven relapsed or refractory non-Hodgkin's lymphoma subjects for which there is no available standard therapy or therapy which may provide clinical benefit.
- Measurable disease (at least 1 lesion ≥ 1.5 cm).
- Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter.
- Systemic corticosteroids within 2 weeks, except low dose regimens which may continue if unchanged.
- Received any radiopharmaceutical therapy within the past six weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00848601
|Los Angeles, California, United States, 90095-1678 |
|Cancer Therapy Research Center
|San Antonio, Texas, United States, 78229 |
|Royal Marsden Hospital
|Sutton, England, United Kingdom, SM2 5PT |
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||February 19, 2009
||December 1, 2011
||United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Keywords provided by Astex Pharmaceuticals:
Hormone & Docetaxel refractory Prostate Cancer
Refractory non-Hodgkin's Lymphoma
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 21, 2013
Neoplasms by Histologic Type
Immune System Diseases
Genital Neoplasms, Male
Neoplasms by Site
Genital Diseases, Male